We plan continued efforts toward the design and pharmacological characterization of more potent and specific antagonists of responses to the neurohypophysial hormones. A major goal is to develop effective antagonists of the antidiuretic response in vivo. These will be useful as pharmacological probes in studies on the contribution of the antidiuretic hormone to water retention under various physiological and pathological conditions. Antagonists of the antidiuretic response could have great value for the treatment of patients suffering dilutional hyponatremia due to inappropriate secretion of ADH. We will also extend our efforts to design more potent and specific antagonists of the vasopressor and oxytocic responses to neurohypophysial hormones. These antagonists will be ued to assess the influence of endogenous ADH and oxytocin on blood pressure regulation and parturition. We also plan continued studies on the influence of endogenous opioids on the release of ADH and oxytocin. We will use isolated hypothalamo-neurohypophysial systems and injections of opiates and endorphins into the cerebral ventricles of intact animals. We will explore the effects of narcotic antagonists on the release of ADH and oxytocin in response to physiological stimuli in an attempt to determine whether endogenous opioids particpate in the physiological regulation of the release of neurohypophysial hormones.